The human anaphylatoxins C3a and C5a are small polypeptides generated through activation of the serum complement cascade by immune or nonimmune stimuli. These endogenous mediators of acute inflammation stimulate the release of vasoactive amines from leucocytes, contraction of smooth muscle, and increased vascular permeability. C5a also chemotactically directs leucocytes towards the inflammatory site. These mechanisms are important for initiation and amplification of inflammatory response in the lung. Recently we have synthesized and tested many short peptides that show the inflammatory activity and specificity of C3a. Related peptides show the spasmogenic activity of C5a or chemotactic activity. This project will continue to explore the mechanisms of action and metabolic fates of these synthetic anaphylatoxin peptides. Radiololabeled peptides will be prepared that mimic or inhibit the anaphylatoxins. Metabolically resistant ones will be made to aid studies of the pathophysiology and inflammation in lung tissue and perfused lung preparations. Radiolabeled and photoreactive peptides will be used for covalently affinity labeling, isolating, and characterizing the leucocyte receptors for C3a and C5a anaphylatoxins. These agents will be prepared by the solid-phase method of peptide synthesis.